title: CD8+ T cell-induced expression of tissue inhibitor of metalloproteinses-1 exacerbated osteoarthritis.
abstract: Despites the fact that T cells are involved in the pathogenesis of osteoarthritis (OA) little is known about the roles of CD8+ T cells in this disease. We investigated the effects of CD8+ T cells and the expression of tissue inhibitor of metalloproteinases 1 (TIMP-1) on joint pathology. Using anterior cruciate ligament-transection (ACLT), OA was induced in mice. The knee joints were histologically assessed for manifestations of OA. The CD8+ T cells from splenocytes and synovium were flow-cytometrically and immunochemically evaluated, respectively. Local expression of TIMP-1, matrix metalloproteinase (MMP)-13, and VEGF were examined. Cartilage degeneration was slower in CD8+ T cell knockout mice than in control mice. CD8+ T cells were activated once OA was initiated and expanded during OA progression. More CD8+ T cells from splenocytes expressed TIMP-1 in ACLT-group mice than in Sham-group mice. The number of TIMP-1-expressing CD8+ T cells in OA mice correlated with the disease severity. TIMP-1 expression in cartilage was co-localized with that of MMP-13 and VEGF. TIMP-1 protein was detected in synovium in which angiogenesis occurred. During the pathogenesis of OA, the expression of TIMP-1, VEGF and MMP-13 accompanying with CD8+ T cells activation were increased. Furthermore, inhibiting the expression of TIMP-1 in joints could retard the progression of OA.
authors.affiliation: Department of Nursing, Chung Hwa University of Medical Technology, Tainan 717, Taiwan. bcshen58@yahoo.com.tw.
authors.forename: Jeng-Long
authors.initials: JL
authors.lastname: Hsieh
authors.forename: Ai-Li
authors.initials: AL
authors.lastname: Shiau
authors.forename: Che-Hsin
authors.initials: CH
authors.lastname: Lee
authors.forename: Shiu-Ju
authors.initials: SJ
authors.lastname: Yang
authors.forename: Bih-O
authors.initials: BO
authors.lastname: Lee
authors.forename: I-Ming
authors.initials: IM
authors.lastname: Jou
authors.forename: Chao-Liang
authors.initials: CL
authors.lastname: Wu
authors.forename: Shun-Hua
authors.initials: SH
authors.lastname: Chen
authors.forename: Po-Chuan
authors.initials: PC
authors.lastname: Shen
mesh_terms: D000818:Animals; D016118:Anterior Cruciate Ligament / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002356:Cartilage / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D051379:Mice; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology*; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C560825:Timp1 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse